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Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia (RETONIC)

Primary Purpose

Schizophreniform Catatonia, Treatment Resistant

Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Individualized rTMS on VERUM 1's region or network
Individualized rTMS on VERUM 2's region or network
Individualized rTMS on PLACEBO region
Individualized rTMS on VERUM 1's region or network
Individualized rTMS on VERUM 2's region or network
Individualized rTMS on PLACEBO region
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophreniform Catatonia focused on measuring Precision Medicine, Functional Neuroimaging, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation, Monocentric, Comparative balanced, randomized, double-blind cross-over 3 Arms Study

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Aged from 18 to 70 Y
  • Affiliated to the health insurance
  • Having signed an informed consent
  • Suffering from catatonia according to the DSM5, unremitted since > 2Y
  • Unresponsive or incomplete remission after at least one trial of benzodiazepine and/or Electroconvulsivotherapy
  • Treatment stable for > 6 weeks

Exclusion criteria:

  • Contraindication for MRI, rTMS or tDCS: non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump clip or vascular stent, heart valve or ventricular shunt, seizure disorders, skin pathology in the region of tDCS electrode placement.
  • Pregnancy
  • Severe and non-stabilized somatic pathology
  • Patients deprived of liberty or hospitalized without their consent
  • Patients unable to give informed consent.

Sites / Locations

  • CEMNIS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Verum 1 - Premotor

Verum 2 - Prefrontal

Placebo

Arm Description

The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. The network including the premotor region will be targeted. The therapeutic protocol will be design to correct the rCBF anomaly.

The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. The network including the prefrontal region will be targeted. The therapeutic protocol will be design to correct the rCBF anomaly.

Stimulation of a region with normal rCBF and putatively unrelated to catatonic symptoms (parietal cortex).

Outcomes

Primary Outcome Measures

Clinical global impression (change in severity and improvement)
Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention

Secondary Outcome Measures

Change in personalized daily visual analogical scales assessing the core symptoms.
This scale has been validated
Change in Bush and Francis Catatonia Rating Scale.
This scale has been validated.
Change in psychosis: PANSS.
This scale has been validated.
Change in depression: Calgary Depression Scale.
This scale has been validated.
Change in apathy: actimetry, apathy inventory and apathy evaluation scale.
This scale has been validated.
Change in obsessive compulsive symptoms: Brief Obsessive Compulsive Scale
This scale has been validated.
Change in obsessive compulsive symptoms: Cambridge-Exeter Repetitive Thought Scale.
This scale has been validated.
Change in quality of life for the patient (SF36)
All these scales have been validated.
Change in the helping person ("Zarit scale")
This scale has been validated.
Change in functioning: Global Assessment of Functioning (GAF scale)
This scale has been validated.
Change in functioning: WHODAS 2.0.
This scale has been validated.

Full Information

First Posted
March 22, 2017
Last Updated
April 19, 2022
Sponsor
University Hospital, Strasbourg, France
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1. Study Identification

Unique Protocol Identification Number
NCT03116425
Brief Title
Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia
Acronym
RETONIC
Official Title
Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia - A Proof of Concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 24, 2017 (Actual)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
June 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Investigators hypothesize that personalizing rTMS targets using functional MRI will allow to improve symptoms of patients suffering from chronic catatonia.
Detailed Description
Two dysfunctional networks or regions will be chosen (verum 1 and 2) based on their abnormal rCBF. In line with the symptoms, dorso-lateral prefrontal and premotor regions are expected to be chiefly concerned. A normal region regarding its rCBF will be used as placebo. Targets will be stimulated using intermittent or continuous theta-burst according to the rCBF anomaly as an attempt to "normalize" their activity. The coil will be positioned using a robotic device under the control of a neuronavigation system in order to deliver a homogeneous stimulation. Using a balanced blinded randomized cross-over design, patients will be stimulated on 5 consecutive days (4 sessions per day) and evaluated pre-, post-stimulation and 1 month after. In this pilot study the primary outcome measures will be the clinical global impression scale whereas MRI will insure that stimulations achieved the correction of the rCBF anomalies. Secondary outcome measures will include personalized target symptom scales, and scales for catatonic, apathic and obsessive-compulsive symptoms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophreniform Catatonia, Treatment Resistant
Keywords
Precision Medicine, Functional Neuroimaging, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation, Monocentric, Comparative balanced, randomized, double-blind cross-over 3 Arms Study

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Verum 1 - Premotor
Arm Type
Experimental
Arm Description
The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. The network including the premotor region will be targeted. The therapeutic protocol will be design to correct the rCBF anomaly.
Arm Title
Verum 2 - Prefrontal
Arm Type
Experimental
Arm Description
The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. The network including the prefrontal region will be targeted. The therapeutic protocol will be design to correct the rCBF anomaly.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Stimulation of a region with normal rCBF and putatively unrelated to catatonic symptoms (parietal cortex).
Intervention Type
Device
Intervention Name(s)
Individualized rTMS on VERUM 1's region or network
Other Intervention Name(s)
Putative premotor region or network
Intervention Description
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
Intervention Type
Device
Intervention Name(s)
Individualized rTMS on VERUM 2's region or network
Other Intervention Name(s)
Putative prefrontal region or network
Intervention Description
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
Intervention Type
Device
Intervention Name(s)
Individualized rTMS on PLACEBO region
Other Intervention Name(s)
(One per line)
Intervention Description
Region will be modulated up or down according to the stimulation protocol used in VERUM 1 and 2 conditions. Stimulation will be replicated up to 5 times per session. Patients will have 4 sessions per day on 5 successive days per arm.
Intervention Type
Procedure
Intervention Name(s)
Individualized rTMS on VERUM 1's region or network
Other Intervention Name(s)
Putative premotor region or network
Intervention Description
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
Intervention Type
Procedure
Intervention Name(s)
Individualized rTMS on VERUM 2's region or network
Other Intervention Name(s)
Putative prefrontal region or network
Intervention Description
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
Intervention Type
Procedure
Intervention Name(s)
Individualized rTMS on PLACEBO region
Intervention Description
Region will be modulated up or down according to the stimulation protocol used in VERUM 1 and 2 conditions. Stimulation will be replicated up to 5 times per session. Patients will have 4 sessions per day on 5 successive days per arm.
Primary Outcome Measure Information:
Title
Clinical global impression (change in severity and improvement)
Description
Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention
Time Frame
In term of percentage reduction in symptoms, difference between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Secondary Outcome Measure Information:
Title
Change in personalized daily visual analogical scales assessing the core symptoms.
Description
This scale has been validated
Time Frame
Points results will be averaged over the 4 days before and after each therapeutic arm.
Title
Change in Bush and Francis Catatonia Rating Scale.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in psychosis: PANSS.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in depression: Calgary Depression Scale.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in apathy: actimetry, apathy inventory and apathy evaluation scale.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in obsessive compulsive symptoms: Brief Obsessive Compulsive Scale
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in obsessive compulsive symptoms: Cambridge-Exeter Repetitive Thought Scale.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in quality of life for the patient (SF36)
Description
All these scales have been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in the helping person ("Zarit scale")
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in functioning: Global Assessment of Functioning (GAF scale)
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Title
Change in functioning: WHODAS 2.0.
Description
This scale has been validated.
Time Frame
Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Other Pre-specified Outcome Measures:
Title
Change of rCBF anomalies
Description
The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). rCBF will be measured using the average of 2 ∙ 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. We will compare the rCBF change of the target region before and after the therapeutic protocol between the different procedures (ANOVA).
Time Frame
Points involvement in scale between before (assessed once between D-7 to -1) and after (assessed once between D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Aged from 18 to 70 Y Affiliated to the health insurance Having signed an informed consent Suffering from catatonia according to the DSM5, unremitted since > 2Y Unresponsive or incomplete remission after at least one trial of benzodiazepine and/or Electroconvulsivotherapy Treatment stable for > 6 weeks Exclusion criteria: Contraindication for MRI, rTMS or tDCS: non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump clip or vascular stent, heart valve or ventricular shunt, seizure disorders, skin pathology in the region of tDCS electrode placement. Pregnancy Severe and non-stabilized somatic pathology Patients deprived of liberty or hospitalized without their consent Patients unable to give informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jack FOUCHER, MD
Organizational Affiliation
Hôpitaux Universitaires de Strasbourg
Official's Role
Principal Investigator
Facility Information:
Facility Name
CEMNIS
City
Strasbourg
ZIP/Postal Code
67091
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia

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